419 research outputs found
Query processing of spatial objects: Complexity versus Redundancy
The management of complex spatial objects in applications, such as geography and cartography,
imposes stringent new requirements on spatial database systems, in particular on efficient
query processing. As shown before, the performance of spatial query processing can be improved
by decomposing complex spatial objects into simple components. Up to now, only decomposition
techniques generating a linear number of very simple components, e.g. triangles or trapezoids, have
been considered. In this paper, we will investigate the natural trade-off between the complexity of
the components and the redundancy, i.e. the number of components, with respect to its effect on
efficient query processing. In particular, we present two new decomposition methods generating
a better balance between the complexity and the number of components than previously known
techniques. We compare these new decomposition methods to the traditional undecomposed representation
as well as to the well-known decomposition into convex polygons with respect to their
performance in spatial query processing. This comparison points out that for a wide range of query
selectivity the new decomposition techniques clearly outperform both the undecomposed representation
and the convex decomposition method. More important than the absolute gain in performance
by a factor of up to an order of magnitude is the robust performance of our new decomposition
techniques over the whole range of query selectivity
Moving Beyond Noninformative Priors: Why and How to Choose Weakly Informative Priors in Bayesian Analyses
Throughout the last two decades, Bayesian statistical methods have proliferated throughout ecology and evolution. Numerous previous references established both philosophical and computational guidelines for implementing Bayesian methods. However, protocols for incorporating prior information, the defining characteristic of Bayesian philosophy, are nearly nonexistent in the ecological literature. Here, I hope to encourage the use of weakly informative priors in ecology and evolution by providing a ‘consumer\u27s guide’ to weakly informative priors. The first section outlines three reasons why ecologists should abandon noninformative priors: 1) common flat priors are not always noninformative, 2) noninformative priors provide the same result as simpler frequentist methods, and 3) noninformative priors suffer from the same high type I and type M error rates as frequentist methods. The second section provides a guide for implementing informative priors, wherein I detail convenient ‘reference’ prior distributions for common statistical models (i.e. regression, ANOVA, hierarchical models). I then use simulations to visually demonstrate how informative priors influence posterior parameter estimates. With the guidelines provided here, I hope to encourage the use of weakly informative priors for Bayesian analyses in ecology. Ecologists can and should debate the appropriate form of prior information, but should consider weakly informative priors as the new ‘default’ prior for any Bayesian model
Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder
Aim: Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD. Materials & methods: We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts participating in the PTSD working group of the Psychiatric Genomics Consortium. Results: Two CpG sites significantly associated with current PTSD in NRG1 (cg23637605) and in HGS (cg19577098). Conclusion: PTSD is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts
Measuring Novel Antecedents of Mental Illness: The Questionnaire of Unpredictability in Childhood
Increasing evidence indicates that, in addition to poverty, maternal depression, and other well-established factors, unpredictability of maternal and environmental signals early in life influences trajectories of brain development, determining risk for subsequent mental illness. However, whereas most risk factors for later vulnerability to mental illness are readily measured using existing, clinically available tools, there are no similar measures for assessing early-life unpredictability. Here we validate the Questionnaire of Unpredictability in Childhood (QUIC) and examine its associations with mental health in the context of other indicators of childhood adversity (e.g., traumatic life events, socioeconomic status, and parenting quality). The QUIC was initially validated through administration to a cohort of adult females (N = 116) and then further refined in two additional independent cohorts (male Veterans, N = 95, and male and female adolescents, N = 175). The QUIC demonstrated excellent internal (α = 0.89) and test–retest reliability (r = 92). Scores on the QUIC were positively correlated with other prospective indicators of exposures to unpredictable maternal inputs in infancy and childhood (unpredictable maternal mood and sensory signals), and accuracy of recall also was confirmed with prospective data. Importantly, the QUIC predicted symptoms of anxiety, depression, and anhedonia in the three study cohorts, and these effects persisted after adjusting for other previously established risk factors. The QUIC, a reliable and valid self-report assessment of exposure to unpredictability in the social, emotional, and physical domains during early life, is a brief, comprehensive, and promising instrument for predicting risk for mental illness
A monolithic MEMS position sensor for closed-loop high-speed atomic force microscopy
The accuracy and repeatability of atomic force microscopy (AFM) imaging significantly depend on the accuracy of the piezoactuator. However, nonlinear properties of piezoactuators can distort the image, necessitating sensor-based closed-loop actuators to achieve high accuracy AFM imaging. The advent of high-speed AFM has made the requirements on the position sensors in such a system even more stringent, requiring higher bandwidths and lower sensor mass than traditional sensors can provide. In this paper, we demonstrate a way for high-speed, high-precision closed-loop AFM nanopositioning using a novel, miniaturized micro-electro-mechanical system position sensor in conjunction with a simple PID controller. The sensor was developed to respond to the need for small, lightweight, high-bandwidth, long-range and sub-nm-resolution position measurements in high-speed AFM applications. We demonstrate the use of this sensor for closed-loop operation of conventional as well as high-speed AFM operation to provide distortion-free images. The presented implementation of this closed-loop approach allows for positioning precision down to 2.1 Å, reduces the integral nonlinearity to below 0.2%, and allows for accurate closed loop imaging at line rates up to 300 Hz
PROC , PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study
Genes encoding protein C anticoagulant pathways are candidates for athero-thrombotic and other aging-related disorders
Longitudinal analyses of the DNA methylome in deployed military servicemen identify susceptibility loci for post-traumatic stress disorder
In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions. Evidence for mediation of the relation between combat trauma and PTSD symptoms by longitudinal changes in DNA methylation was observed at several positions and regions. Bioinformatic analyses of the reported associations identified significant enrichment in several pathways relevant for symptoms of PTSD. Targeted analyses of the significant findings from the discovery sample in an independent prospective cohort of male US marines (n=98) replicated the observed relation between decreases in DNA methylation levels and PTSD symptoms at genomic regions in ZFP57, RNF39 and HIST1H2APS2. Together, our study pinpoints three novel genomic regions where longitudinal decreases in DNA methylation across the period of exposure to combat trauma marks susceptibility for PTSD
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International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations
A Survey of Genomic Studies Supports Association of Circadian Clock Genes with Bipolar Disorder Spectrum Illnesses and Lithium Response
Circadian rhythm abnormalities in bipolar disorder (BD) have led to a search for genetic abnormalities in circadian “clock genes” associated with BD. However, no significant clock gene findings have emerged from genome-wide association studies (GWAS). At least three factors could account for this discrepancy: complex traits are polygenic, the organization of the clock is more complex than previously recognized, and/or genetic risk for BD may be shared across multiple illnesses. To investigate these issues, we considered the clock gene network at three levels: essential “core” clock genes, upstream circadian clock modulators, and downstream clock controlled genes. Using relaxed thresholds for GWAS statistical significance, we determined the rates of clock vs. control genetic associations with BD, and four additional illnesses that share clinical features and/or genetic risk with BD (major depression, schizophrenia, attention deficit/hyperactivity). Then we compared the results to a set of lithium-responsive genes. Associations with BD-spectrum illnesses and lithium-responsiveness were both enriched among core clock genes but not among upstream clock modulators. Associations with BD-spectrum illnesses and lithium-responsiveness were also enriched among pervasively rhythmic clock-controlled genes but not among genes that were less pervasively rhythmic or non-rhythmic. Our analysis reveals previously unrecognized associations between clock genes and BD-spectrum illnesses, partly reconciling previously discordant results from past GWAS and candidate gene studies
Division site selection linked to inherited cell surface wave troughs in mycobacteria
Cell division is tightly controlled in space and time to maintain cell size and ploidy within narrow bounds. In bacteria, the canonical Minicell (Min) and nucleoid occlusion (Noc) systems together ensure that division is restricted to midcell after completion of chromosome segregation1. It is unknown how division site selection is controlled in bacteria that lack homologues of the Min and Noc proteins, including mycobacteria responsible for tuberculosis and other chronic infections2. Here, we use correlated optical and atomic-force microscopy3,4 to demonstrate that morphological landmarks (waveform troughs) on the undulating surface of mycobacterial cells correspond to future sites of cell division. Newborn cells inherit wave troughs from the (grand)mother cell and ultimately divide at the centre-most wave trough, making these morphological features the earliest known landmark of future division sites. In cells lacking the chromosome partitioning (Par) system, missegregation of chromosomes is accompanied by asymmetric cell division at off-centre wave troughs, resulting in the formation of anucleate cells. These results demonstrate that inherited morphological landmarks and chromosome positioning together restrict mycobacterial division to the midcell position
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